As an analgesic, a narcotic analgesic (such as morphine), a non-narcotic analgesic (such as aspirin or indomethacin) or a narco-antagonistic analgesic (such as pentazocine) is employed. A narcotic analgesic exerts its analgesic effect mainly by inhibiting a central algesic excitatory transmission. A non-narcotic analgesic exerts its analgesic effect mainly by inhibiting the production of a peripheral dolorogenic substance. A narco-antagonistic analgesic exerts its analgesic effect in a mechanism similar to that of a narcotic analgesic.
However, there is no analgesic which is effective against a chronic pain which is not suppressed by morphine, an allodynia accompanied with herpes zoster or a hyperalgesia, and an excellent analgesic has been desired to be created.
Nociceptin is a neuropeptide related to various nervous activities including an in vivo algesia. JP 10-212290 A describes that a nociceptin agonist and/or antagonist may be effective in treating a mental disorder, neuropathy and physiological disorder, and particularly effective in ameliorating anxiety and stress disorder, depression, traumatic disorder, amnesia due to Alzheimer's disease or other dementia, symptoms of epilepsy and spasm, acute and/or chronic pain, drug abuse withdrawal symptoms, water balance control, Na+ excretion, arterial blood pressure disorder, and eating disorder such as an obesity.
As a non-peptide compound acting on a nociceptin receptor, lofentanil, naloxone benzoylhydrazone and 2-oxoimidazole derivative (WO98/54168) are known. However, these compounds are still at the stage of a basic research, and none of them has been commercially available.
Various quinazoline derivatives relating to a Compound (I) according to the present invention are known (WO93/07124, JP 2923742, WO98/50370, WO99/09986, JP 47-2927 A). Among such derivatives, 4-phenylmethylamino-2-[2-(3-pyridyl) vinyl]quinazoline disclosed in JP 2923742 is reported to have a cyclic GMP-phosphodiesterase inhibiting effect or thromboxan A2 (TXA2) synthetase inhibiting effect and to be useful in the prophylaxis and/or treatment of inflammations, hypertension, thrombosis, arterial sclerosis, cerebral hemorrhage, asthma, myocardial infarction, angina pectoris, cerebral infarction and the like. 4-(2-dimethylaminoethylamino)-6,7-dimethoxy-2-(E)-styrylquinazoline or 6,7-dimethoxy-4-[N-methyl-N-(3-dimethylamino) propylamino]-2-(E)-styrylquinazoline disclosed in WO99/09986 is reported to be useful as an insulin secretion promoter or diabetes treating agent. JP 47-2927 A describes that 4-(4-diethylamino-1-methyl) butylamino-2-(E)-(4-chlorostyryl) quinazoline is useful as an anti-inflammatory agent and the like.